ORCID Profile
0000-0001-7221-6706
Current Organisations
University of Zurich
,
Universität Zürich
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Publisher: Elsevier BV
Date: 2012
DOI: 10.1016/J.BBRC.2011.12.044
Abstract: The herpes simplex virus type 1 (HSV-1) structural tegument protein pUL37, which is conserved across the Herpesviridae family, is known to be essential for secondary envelopment during the egress of viral particles. To shed light on additional roles of pUL37 during viral replication a yeast two-hybrid screen of a human brain cDNA library was undertaken. This screen identified ten host cell proteins as potential pUL37 interactors. One of the interactors, serine threonine kinase TAOK3, was subsequently confirmed to interact with pUL37 using an in vitro pulldown assay. Such host cell UL37 interactions provide further insights into the multifunctional role of this herpesviral tegument protein.
Publisher: Elsevier BV
Date: 11-2009
DOI: 10.1016/J.VIRUSRES.2009.07.007
Abstract: Herpes virions consist of four morphologically distinct structures, a DNA core, capsid, tegument, and envelope. Tegument occupies the space between the nucleocapsid (capsid containing DNA core) and the envelope. A combination of genetic, biochemical and proteomic analysis of alphaherpes virions suggest the tegument contains in the order of 20 viral proteins. Historically the tegument has been described as amorphous but increasing evidence suggests there is an ordered addition of tegument during assembly. This review highlights the erse roles, in addition to structural, that tegument plays during herpes viral replication using as an ex le herpes simplex virus type 1. Such erse roles include: capsid transport during entry and egress targeting of the capsid to the nucleus regulation of transcription, translation and apoptosis DNA replication immune modulation cytoskeletal assembly nuclear egress of capsid and viral assembly and final egress.
Publisher: Elsevier BV
Date: 2012
DOI: 10.1016/J.VIROL.2011.11.002
Abstract: The herpes simplex virus type 1 (HSV-1) structural tegument proteins pUL36 and pUL37 are essential for secondary envelopment during the egress of viral particles. For this study, scanning alanine mutagenesis of HSV-1 pUL37, in combination with yeast two-hybrid, identified pUL37 residue D631 as a major determinant for binding of pUL36. Further analysis of the binding of this pUL37 mutant to pUL36 by coimmunoprecipitation assay confirmed the role of pUL37 D631 in mediating binding of pUL36. A trans-complementation assay using pUL37 deletion virus FRΔUL37 was then carried out, where pUL37 wild type or D631A were provided in trans. For pUL37 D631A, a significant reduction in virus titer was observed compared to that seen when pUL37 wild type was present. The results presented here underline the crucial role of the pUL36 UL37 interaction in replication of HSV-1 and indicate a critical role for pUL37 D631 in mediating this interaction.
Publisher: Elsevier BV
Date: 04-2014
DOI: 10.1016/J.VIROL.2014.02.003
Abstract: The herpes simplex virus type 1 (HSV-1) tegument proteins pUL36 (VP1/2) and pUL37 are essential for viral egress. We previously defined a minimal domain in HSV-1 pUL36, residues 548-572, as important for binding pUL37. Here, we investigated the role of this region in binding to pUL37 and facilitating viral replication. We deleted residues 548-572 in frame in a virus containing a mRFP tag at the N-terminus of the capsid protein VP26 and an eGFP tag at the C-terminus of pUL37 (HSV-1pUL36∆548-572). This mutant virus was unable to generate plaques in Vero cells, indicating that deletion of this region of pUL36 blocks viral replication. Imaging of HSV-1pUL36∆548-572-infected Vero cells, in comparison to parental and resucant, revealed a block in secondary envelopment of cytoplasmic capsids. In addition, immunoblot analysis suggested that failure to bind pUL37 affected the stability of pUL36. This study provides further insight into the role of this essential interaction.
Publisher: Proceedings of the National Academy of Sciences
Date: 26-10-1999
Abstract: This study aimed to exploit bacterial artificial chromosomes (BAC) as large antigen-capacity DNA vaccines (BAC-VAC) against complex pathogens, such as herpes simplex virus 1 (HSV-1). The 152-kbp HSV-1 genome recently has been cloned as an F-plasmid-based BAC in Escherichia coli (fHSV), which can efficiently produce infectious virus progeny upon transfection into mammalian cells. A safe modification of fHSV, fHSVΔpac, does not give rise to progeny virus because the signals necessary to package DNA into virions have been excluded. However, in mammalian cells fHSVΔpac DNA can still replicate, express the HSV-1 genes, cause cytotoxic effects, and produce virus-like particles. Because these functions mimic the lytic cycle of the HSV-1 infection, fHSVΔpac was expected to stimulate the immune system as efficiently as a modified live virus vaccine. To test this hypothesis, mice were immunized with fHSVΔpac DNA applied intradermally by gold-particle bombardment, and the immune responses were compared with those induced by infection with disabled infectious single cycle HSV-1. Immunization with either fHSVΔpac or disabled infectious single cycle HSV-1 induced the priming of HSV-1-specific cytotoxic T cells and the production of virus-specific antibodies and conferred protection against intracerebral injection of wild-type HSV-1 at a dose of 200 LD 50 . Protection probably was cell-mediated, as transfer of serum from immunized mice did not protect naive animals. We conclude that BAC-VACs per se , or in combination with genetic elements that support replicative lification of the DNA in the cell nucleus, represent a useful new generation of DNA-based vaccination strategies for many viral and nonviral antigens.
No related grants have been discovered for Cornel Fraefel.